Attività fisica, composizione corporea e sensibilità gustativa nei pazienti affetti da malattia di Parkinson

La malattia di Parkinson (Parkinson’s Disease PD) è generalmente considerato un disturbo motorio, ma possono esserci caratteristiche non motorie e sensoriali associate. Per questo motivo, l’attenzione di questo progetto di dottorato è stata focalizzata sul ruolo che potrebbe avere l’attività fisica, la sensibilità gustativa e la composizione corporea nei pazienti affetti da PD. Lo scopo della prima parte della tesi è stato quello di indagare l’effetto che l’esercizio fisico può avere sull’α-syntot, in quanto marcatore di progressione della malattia, e su altri marcatori biologici di infiammazione quali il TNF-α e IL10 sia salivari che plasmatici, e il cortisolo salivare, in pazienti affetti da PD idiopatica. I pazienti reclutati sono stati suddivisi in due gruppi, gruppo controllo (CG) e gruppo sperimentale sottoposto a treadmill training (RehabG). Il miglioramento delle misure di outcome di performance motoria al termine delle quattro settimane di allenamento ha dimostrato l’efficacia del protocollo aerobico in quanto i pazienti trattati rispetto a quelli sedentari hanno ottenuto punteggi migliori ai tests di resistenza fisica, di valutazione dell’equilibrio e del rischio di caduta. Al termine delle settimane di allenamento aerobico è stato notato un impatto più significativo sui livelli di marcatori biologici testati, e soprattutto per le citochine salivari, TNF-α e IL10, sono risultate in concentrazioni diminuite nel gruppo RehabG rispetto al gruppo CG. Invece, è risultata meno significativa la correlazione con i livelli dell’α-syntot. Trattandosi di uno studio pilota, saranno necessarie ulteriori ricerche che permetteranno di chiarire quali protocolli di attività fisica potranno modulare la progressione della malattia, e inoltre chiarire anche il ruolo dei marcatori biologici nel monitoraggio del danno biologico nella PD. Lo scopo della seconda parte dello studio è stato quello di indagare meglio alcuni aspetti della correlazione esistente tra PD e la sensibilità gustativa e determinare in qualche modo una modificazione dell’assunzione dei nutrienti tale da provocare uno stato di malnutrizione, e se ci sia una modificazione della composizione corporea. Lo studio è stato condotto arruolando 56 pazienti affetti da PD idiopatico, confrontati con 88 controlli sani. Per la valutazione della sensibilità gustativa sono stati impiegati tamponi di cotone impregnati con una soluzione contenente una sostanza gustativa in 4 diverse concentrazioni per ciascuno dei 4 gusti base (salato, dolce, acido, amaro), con l’aggiunta di olio di colza puro e acqua deionizzata. È stata analizzata anche la composizione corporea. La popolazione appartenente al gruppo PD ha mostrato difficoltà nel discriminare il gusto in circa il 50% dei casi. Questo risultato sembrava in gran parte dipendente dall'età e dal sesso e non è significativamente diverso dai punteggi ottenuti dal gruppo controllo di pari età e sesso. La sensibilità gustativa non dipendeva inoltre dalla durata o dalla gravità della malattia. La composizione corporea del gruppo PD si discostava significativamente dai controlli: i pazienti del gruppo PD pesano meno dei soggetti del gruppo controllo di pari età e mostrano una massa magra (FFM) e acqua corporea totale (TBW) significativamente inferiore. Le abitudini alimentari affidate al caregiver non sono diverse dai controlli e la dieta seguita è quella Mediterranea. Non è emerso chiaramente che l’ageusia sia un biomarcatore candidato della malattia, ma il monitoraggio della composizione corporea e del peso possono essere delle misure semplici ed efficaci per seguire la progressione della malattia e il rischio di deterioramento funzionale nella fase avanzata.Parkinson's disease (PD) is generally considered a motor disorder, but it can also involve non-motor and sensory symptoms. For this reason, this doctoral project was focused on the role that physical activity, taste perception and body composition could have in patients with PD. The aim of the first part of this thesis was to investigate the effect that physical exercise can have on α-syntot, as a marker of disease progression, and on other biological markers of inflammation such as both salivary and plasma TNF-α and IL10, and salivary cortisol, in patients with idiopathic PD. The recruited patients were divided into two groups, the control group (CG) and the experimental group undergoing treadmill training (RehabG). The improvement of the motor performance outcome measures at the end of the four weeks of training demonstrated the efficacy of the aerobic protocol in that the treated patients obtained better scores in physical endurance tests, balance and risk of falling compared to the sedentary ones. At the end of the weeks of aerobic training, more significant impact was noted on the levels of biological markers tested, and especially for the salivary cytokines, TNF-α and IL10, which resulted in decreased concentrations in the RehabG group compared to the CG group. However, the correlation with α-syntot levels was less significant. As this is a pilot study, further research will be needed which will allow to clarify which physical activity protocols can modulate the progression of the disease, and also to clarify the role of biological markers in monitoring biological damage in PD. The aim of the second part of the study was to better investigate some aspects of the correlation between PD and taste perception to clarify and somehow determine a modification of nutrient intake such as to cause a state of malnutrition, and whether there is a change in body composition. The study was conducted by enrolling 56 patients with idiopathic PD, compared with 88 healthy controls. For the evaluation of taste perception were used cotton swabs impregnated with a solution containing a tasting substance in 4 different concentrations for each of the 4 basic flavors (salty, sweet, sour, bitter), with the addition of pure rapeseed oil and deionized water. Body composition was also analysed. The population belonging to the PD group showed difficulty in discriminating taste in about 50% of cases. This result appeared to be largely age- and sex-related and did not differ significantly from the age- and sex-matched control group scores. Taste perception was also not dependent on the duration or severity of the disease. The body composition of the PD group differed significantly from the controls: PD patients weigh less than age-matched control subjects and show significantly lower free fat mass (FFM) and total body water (TBW). The eating habits entrusted to the caregiver are no different from the controls and patients follow a Mediterranean diet. Ageusia did not emerge clearly as a candidate to be a state-trait marker, but monitoring body composition and weight may be simple and effective to follow the disease progression and risk of functional deterioration in the advanced stage

The Role of Oxidative Stress in Autism Spectrum Disorder: A Narrative Literature Review

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder that comprises a complex aetiology, where a genetic component has been suggested, together with multiple environmental risk factors. Because of its increasing incidence in the paediatric population and the lack of successful curative therapies, ASD is one of the most puzzling disorders for medicine. In the last two decades and more, the relationship between oxidative stress (OS) and ASD has been recurrently documented. For this reason, the former hypothesis, according to which reactive oxygen and nitrogen species (ROS and RNS) play an important role in ASD, is now a certainty. Thus, in this review, we will discuss many aspects of the role of OS in ASD. In addition, we will describe, in the context of the most recent literature, the possibility that free radicals promote lipid peroxidation, as well as an increase in other OS biomarkers. Finally, we will outline the possibility of novel nutritional interventions aimed at counteracting ROS production in people with ASD. In fact, new strategies have investigated the possibility that ASD symptoms, as well behavioral anomalies, may be improved after interventions using antioxidants as supplements or included in foods

The Influence of Age and Oral Health on Taste Perception in Older Adults: A Case-Control Study

Declining gustatory function, nutrition, and oral health are important elements of health in older adults that can affect the aging process. The aim of the present work was to investigate the effect of age and oral status on taste discrimination in two different groups of elderly subjects living either in an Italian residential institution (TG) or in the community (CG). A total of 90 subjects were enrolled in the study (58 CG vs. 32 TG). Masticatory performance (MP) was assessed using the two-color mixing ability test. Taste function was evaluated using cotton pads soaked with six taste stimuli (salty, acid, sweet, bitter, fat and water). A positive correlation between age and missing teeth (r = 0.51, C.I. [0.33; 0.65], p p p p p < 0.05). The best understanding of the relationship between MP, taste sensitivity, and nutritional factors is a necessary criterion for the development of new therapeutic strategies to address more effectively the problems associated with malnutrition in elderly subjects

Treatment-Related Dysgeusia in Oral and Oropharyngeal Cancer: A Comprehensive Review

Oral cancer is the most common tumor of the head and neck region. Its management is based on surgical and systemic therapies. Taste disorders represent the most common side effect of these treatments; indeed, dysgeusia is noted by 70% of oral cancer patients. Despite survival remaining the primary endpoint of cancer patients, taste impairments can cause psychological distress. This comprehensive review describes the last decade’s knowledge from the literature regarding taste alterations in patients with oral and oropharyngeal squamous cell carcinoma. A total of 26 articles in English, including prospective, cross-sectional, and case–control studies, and clinical trials were evaluated. Literature analysis shows that anti-cancer treatments can destroy taste cells, decrease and alter their receptors, and interrupt nerve transmission. Furthermore, the tumour itself can destroy the oral mucosal lining, which encloses the taste buds. Dysgeusia typically occurs in 3–4 weeks of treatments, and usually taste sensation is recovered within 3–12 months. However, some patients exhibit incomplete or no recovery, even several years later. Thus, dysgeusia can become a chronic issue and negatively influence patients’ quality of life, worsening their dysphagia and their nutritional status. Physicians should be focused on preventing oncological treatment-related symptoms, offering the most suitable personalized support during therapy

Multiple Sclerosis: Inflammatory and Neuroglial Aspects

Multiple sclerosis (MS) represents the most common acquired demyelinating disorder of the central nervous system (CNS). Its pathogenesis, in parallel with the well-established role of mechanisms pertaining to autoimmunity, involves several key functions of immune, glial and nerve cells. The disease&rsquo;s natural history is complex, heterogeneous and may evolve over a relapsing-remitting (RRMS) or progressive (PPMS/SPMS) course. Acute inflammation, driven by infiltration of peripheral cells in the CNS, is thought to be the most relevant process during the earliest phases and in RRMS, while disruption in glial and neural cells of pathways pertaining to energy metabolism, survival cascades, synaptic and ionic homeostasis are thought to be mostly relevant in long-standing disease, such as in progressive forms. In this complex scenario, many mechanisms originally thought to be distinctive of neurodegenerative disorders are being increasingly recognized as crucial from the beginning of the disease. The present review aims at highlighting mechanisms in common between MS, autoimmune diseases and biology of neurodegenerative disorders. In fact, there is an unmet need to explore new targets that might be involved as master regulators of autoimmunity, inflammation and survival of nerve cells

Pathogenic Role of the Sphingosine 1-Phosphate (S1P) Pathway in Common Gynecologic Disorders (GDs): A Possible Novel Therapeutic Target

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid, noteworthy for its involvement both in the modulation of various biological processes and in the development of many diseases. S1P signaling can be either pro or anti-inflammatory, and the sphingosine kinase (SphK)-S1P-S1P receptor (S1PR) axis is a factor in accelerating the growth of several cells, including endometriotic cells and fibrosis. Gynecologic disorders, including endometriosis, adenomyosis, and uterine fibroids are characterized by inflammation and fibrosis. S1P signaling and metabolism have been shown to be dysregulated in those disorders and they are likely implicated in their pathogenesis and pathophysiology. Enzymes responsible for inactivating S1P are the most affected by the dysregulation of S1P balanced levels, thus causing accumulation of sphingolipids within these cells and tissues. The present review highlights the past and latest evidence on the role played by the S1P pathways in common gynecologic disorders (GDs). Furthermore, it discusses potential future approaches in the regulation of this signaling pathway that could represent an innovative and promising therapeutical target, also for ovarian cancer treatment

Multiple Sclerosis: Inflammatory and Neuroglial Aspects

Multiple sclerosis (MS) represents the most common acquired demyelinating disorder of the central nervous system (CNS). Its pathogenesis, in parallel with the well-established role of mechanisms pertaining to autoimmunity, involves several key functions of immune, glial and nerve cells. The disease’s natural history is complex, heterogeneous and may evolve over a relapsing-remitting (RRMS) or progressive (PPMS/SPMS) course. Acute inflammation, driven by infiltration of peripheral cells in the CNS, is thought to be the most relevant process during the earliest phases and in RRMS, while disruption in glial and neural cells of pathways pertaining to energy metabolism, survival cascades, synaptic and ionic homeostasis are thought to be mostly relevant in long-standing disease, such as in progressive forms. In this complex scenario, many mechanisms originally thought to be distinctive of neurodegenerative disorders are being increasingly recognized as crucial from the beginning of the disease. The present review aims at highlighting mechanisms in common between MS, autoimmune diseases and biology of neurodegenerative disorders. In fact, there is an unmet need to explore new targets that might be involved as master regulators of autoimmunity, inflammation and survival of nerve cells

The ALA5/ALA6/ALA7 repeat polymorphisms of the glutathione peroxidase-1 (GPx1) gene and autism spectrum disorder

: Autism is a severe neurodevelopmental disorder leading to deficits in social interaction, communication, and several activities. An increasing number of evidence suggests a role of oxidative stress in the etiology of autism spectrum disorder (ASD). Indeed, impaired antioxidant mechanisms may lead to the inadequate removal of H2 O2 with a consequent increase in highly active hydroxyl radicals and other reactive oxygen species causing cellular damages. The GPx1 is one of the most important enzymes counteracting oxidative stress. In this work, we investigated a possible correlation between the GCG repeat polymorphism present in the first exon of GPx1 gene encoding a tract of five to seven alanine residues (ALA5, ALA6, and ALA7) and ASD. Our findings highlighted a high frequency of ALA5 allele in ASD subjects. Moreover, proteins corresponding to the three GPx1 variants were produced in vitro, and the evaluation of their activity showed a lower values for GPx1 having ALA5 polymorphism. The comparison of the secondary and tertiary structure predictions revealed an alpha-helix in correspondence of alanine stretch only in the case of GPx1-ALA7 variant. Finally, to better investigate protein structure, steady-state fluorescence measurements of GPx1 intrinsic tryptophan were carried out and the three tested proteins exhibited a different stability under denaturing conditions. This work demonstrates the importance in adopting a multidisciplinary strategy to comprehend the role of GPx1 in ASD